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Introduction Capillaroscopy is a simple method of nailfold capillary imaging, used to diagnose diseases from the systemic sclerosis spectrum. However, the assessment of the capillary image is time-consuming and subjective. This makes it difficult to use for a detailed comparison of studies assessed by various physicians. This pilot study aimed to validate software used for automatic capil­lary counting and image classification as normal or pathological. Material and methods The study was based on the assessment of 200 capillaroscopic images obtained from patients suffering from systemic sclerosis or scleroderma spectrum diseases and healthy people. Dinolite MEDL4N Pro was used to perform capillaroscopy. Each image was analysed manually and described using working software. The neural network was trained using the fast.ai library (based on PyTorch). The ResNet-34 deep residual neural network was chosen; 10-fold cross-validation with the validation and test set was performed, using the Darknet-YoloV3 state of the art neural network in a GPU-optimized (P5000 GPU) environment. For the calculation of 1 mm capillaries, an additional detection mechanism was designed. Results The results obtained under neural network training were compared to the results obtained in manual analysis. The sensitivity of the automatic tool relative to manual assessment in classification of correct vs. pathological images was 89.0%, specificity 89.4% for the training group, in validation 89.0% and 86.9% respectively. For the average number of capillaries in 1 mm the precision of real images detected within the region of interest was 96.48%. Conclusions The pilot software for fully automatic capillaroscopic image assessment can be a useful tool for the rapid classification of a normal and altered capillaroscopy pattern. In addition, it allows one to quickly calculate the number of capillaries. In the future, the tool will be developed and will make it possible to obtain full imaging characteristics independent of the experience of the examiner.

Introduction Idiopathic inflammatory myopathies (IIMs) are a group of systemic connective tissue diseases that present with muscular and extra-muscular manifestations. There are few reports on kidney involvement, especially in dermatomyositis (DM) patients. We evaluated the clinical, laboratory, capillaroscopy, and kidney pathology of patients with DM, who presented with proteinuria during the first year, and followed them for response to treatment. Material and methods We evaluated 205 patients with proximal muscle weakness or high muscle enzymes, who referred to the nailfold capillaroscopy clinic from April 2010 to October 2021. Seventy-four patients fulfilled the New 2017 EULAR/ACR Classification Criteria for adult and juvenile IM with probability of ≥ 90% for DM with duration of ≤ 12 months and proteinuria > 350 mg/24 hours. All manifestations of patients with glomerulopathy and their kidney biopsies were reviewed, and they were followed for their treatment response. Results From 74 patients with DM, 52 female and 22 male, median age 37 (19–65) years, and disease duration of median 4.5 (1–12) months, 2 (2.7%) patients (25- and 28-year-old male) had proteinuria. Their kidney biopsy showed mesangioproliferative glomerulonephritis (GN). There was no case of acute or chronic kidney damage or rhabdomyolysis. Both had high disease activity, high erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), abnormal capillaroscopy, and high anti-Ro positivity with good early response of their kidney function, muscle weakness, and laboratory tests after immunosuppressive treatment for 3–6 months. One patient had capillaroscopy follow-up, and all abnormalities were resolved in 8 fingers. One patient, due to poor follow-up, after 8 months had recurrence of his disease. Conclusions We found mesangioproliferative GN as a rare extra-muscular manifestation in patients with DM in the active and early phase of the disease. Full immunosuppressive treatment showed early complete recovery in these patients.

Objective To assess the longitudinal changes in nailfold videocapillaroscopy (NVC) in patients expressing myositis-specific autoantibodies [anti-aminoacyl-tRNA synthetase (ARS), anti-transcriptional intermediary factor 1 (TIF1), and anti-melanoma differentiation-associated gene 5 (MDA5)]. Methods This study was performed retrospectively, at a single site, on an observational cohort. Seventy-one idiopathic inflammatory myopathy patients were included (25 patients expressed anti-MDA5 Abs, 24 patients expressed anti-TIF1 Abs, and 22 patients expressed anti-ARS Abs). NVC findings included giant, enlarged, and reduced capillaries, haemorrhages, capillary ramification, disorganization of the vascular array, and capillary loss. NVC findings were compared from baseline to after disease activity stabilization. Results The frequency of enlarged capillaries at baseline was different among the three groups, and was significantly higher in patients with anti-TIF1 Abs compared with those with anti-ARS Abs (88% vs 55%, P  < 0.05). Reduced capillaries were significantly increased in patients with anti-TIF1 Abs compared with those with anti-MDA5 (96% vs 44%, P  < 0.0001) or anti-ARS Abs (96% vs 50%, P  < 0.0005). Both enlarged and reduced capillaries improved after stabilization in patients with anti-MDA5 Abs (P  < 0.0001 and P  < 0.05, respectively). These improvements were not observed in patients expressing anti-TIF1 and anti-ARS Abs. However, a significant reduction in haemorrhages was observed in all three groups (P  < 0.0001 for each group). Conclusions The results of this study demonstrate that longitudinal changes in NVC findings may vary depending on myositis-specific Ab expression. Therefore, it is crucial to assess individual NVC findings separately, as each finding may impact disease activity in a different manner. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to quantify nailfold capillary (NFC) abnormalities in anti–melanoma differentiation–associated gene 5 (MDA5) -positive DM patients and to evaluate the association with clinical parameters, including serum biomarkers. In addition, we aimed to clarify the period leading to remission of NFC abnormalities during immunosuppressive treatment in patients with DM. Methods A prospective observational study was conducted including patients (n  = 10) who first visited Hiroshima University Hospital and were diagnosed with DM or clinically amyopathic DM with anti-MDA5 antibodies. We compared the NFC abnormalities detected by nailfold-video capillaroscopy (NVC), physical findings, blood tests, respiratory function tests, and vascular-related growth factors measured using a LEGENDplexTM Multi-Analyte Flow Assay Kit. Results NFC abnormalities improved in all patients from 2 to 17 weeks after the initiation of immunosuppressive treatment. The NVC scores were inversely correlated with anti-MDA5 antibody titres at baseline. NVC scores and forced vital capacity were positively correlated. Baseline values of M-CSF and stem cell factor were correlated with anti-MDA-5 titres. Conclusion Our study suggested that NVC scores and disease activity were inversely correlated before treatment. Vascular-related growth factors, such as M-CSF and stem cell factor, may be associated with the disease mechanism in patients with anti-MDA5 antibody-positive DM. [ABSTRACT FROM AUTHOR]

Objective In patients with RP, capillaroscopy is useful for discriminating primary from secondary causes. There are certain capillaroscopy and lab values as predictive factors leading to a known CTD. We conducted the present study to evaluate the causes of RP in our area and followed the studied subjects to find prognostic factors indicating a definite CTD or remaining a UCTD. Methods In this retrospective cohort study we included all adult patients with RP who were referred for capillaroscopy from 2010 to 2019. All the patients with primary and secondary RP with follow-up were evaluated for demography, laboratory results and capillaroscopy to find the risk factors of their progression to a CTD. Results A total of 760 of 776 patients were included, with 679 being female (89.3%) and 81 (10.7%) male. There were 660 subjects (90.8%) with secondary RP [mostly UCTD (48.2%) and then SSc (16.4%)] and 67 (9.2%) with primary RP; 109 patients were followed up and 42 (42%) of those with secondary RP developed a definite CTD. The scleroderma pattern and some capillary changes on capillaroscopy and/or positive ANA had statistically significant differences for CTD transition. Conclusion We had a small number of patients with primary RP. The most prevalent causes of secondary RP in our patients were UCTD and SSc. Some capillaroscopy and laboratory results alone or in combination could be used as a predictive marker for the transition of patients with UCTD to CTD. [ABSTRACT FROM AUTHOR]

Diabetic sclerodactyly is a frequently recognized skin finding that may occur in patients with diabetes mellitus but coexistence of diabetes and systemic sclerosis is rare. We describe a case of coexistence of type 1 diabetes mellitus and systemic sclerosis in 42-year-old man with the history of Raynaud’s phenomenon, progressive diffuse hardening of the skin and sclerodactyly, slowly worsening with time. The medical history included type 1 diabetes since childhood with microvascular complications. The patient presented a typical capillaroscopic scleroderma-like pattern, antinuclear antibodies and sclerotic lesions in gastrointestinal system. Summing up, our case represents the rare coexistence of autoimmune diseases like diabetes mellitus type 1 and systemic sclerosis.

Objectives Nailfold capillaroscopy is being increasingly used by rheumatologists in the diagnosis of SSc. However, assessment of all nailfolds can be time-consuming in a busy outpatient clinic. Our aim was to answer the question as to how many (and which) fingers a clinician should routinely assess to capture accurately the true state. Methods A total of 2994 assessments (by an international panel of expert observers) of 1600 images from 173 participants (101 with SSc, 22 with primary RP and 50 healthy controls) were included in this analysis. Seven single-finger or finger combinations (derived from the middle and ring fingers) were then tested for sensitivity for the presence of two markers of capillary abnormality [presence of giant capillaries and an SSc grade (early, active or late)] compared with assessment of all eight fingers. Results For the eight-finger gold standard, sensitivity against the diagnostic criteria was 74.6% (53.0% for the presence of giants alone and 73.1% for image grade alone). Examining only one finger gave low sensitivity (ranging from right middle 31.7% to left ring 46.6%). Examining both ring fingers gave a sensitivity of 59.8%, whereas examining the four-finger combination of both ring and both middle fingers gave a sensitivity of 66.7%. Conclusion During routine capillaroscopic examination, ideally all eight nailbeds (excluding thumbs) should be examined, otherwise some abnormalities will be missed. Examining only four fingers reduces capillaroscopy sensitivity. [ABSTRACT FROM AUTHOR]

Objectives. Subgroups of capillaroscopic scleroderma landscape have been correlated with stages of SSc: two groups for Maricq's classification (slow and active), and three for Cutolo's classification (early, active and late). We report inter- and intra-observer agreement for these classifications as a preliminary step in the multicentre prospective SCLEROCAP study, which aims to assess the classification and single capillaroscopic items as prognostic tools for SSc. Methods. SCLEROCAP included 385 patients. Agreement was studied in the first 100 patients, who were independently rated twice by two observers, blind to patients' characteristics; 30 of the patients were rated once by six observers. After consensus meetings, these ratings were held again. Kappa and intraclass correlation coefficients were used to assess agreement. Results. Interobserver agreement on 100 patients was moderate for Maricq and Cutolo classifications [κ 0.47 (0.28, 0.66) and 0.49 (0.33, 0.65), respectively], and became substantial after consensus meetings [0.64 (0.50, 0.77) and 0.69 (0.56, 0.81)]. Intra-observer agreement between two observers was moderate to substantial: κ 0.54 (0.33, 0.75) and 0.70 (0.57, 0.83) for Maricq's classification; 0.57 (0.38, 0.77) and 0.76 (0.65, 0.87) for Cutolo's. Thirty patients were rated once by each of six observers, and agreement was moderate to substantial: κ 0.57 ± 0.10 (Maricq) and 0.61 ± 0.12 (Cutolo). Agreement was substantial for bushy, giant capillaries and microhaemorrhages, moderate for capillary density and low for oedema, disorganization and avascular areas. Conclusion. The moderate reproducibility of Maricq and Cutolo classifications might hamper their prognostic value in SSc patients. Consensus meetings improve reliability, a prerequisite for better prognostic performances. A focus on giant capillaries, haemorrhages and capillary density might be more reliable. [ABSTRACT FROM AUTHOR]

In 1972, Sharp et al. described a new autoimmune rheumatic disease that they called MCTD, characterized by overlapping features of SSc, SLE, PM/DM, high levels of anti-U1snRNP and low steroid requirements with good prognosis. MCTD was proposed as a distinct disease. However, soon after the original description, questions about the existence of such a syndrome as well as disputes over the features initially described began to surface. The conundrum of whether MCTD is a distinct disease entity remains controversial. We undertook a literature review, focusing on the articles reporting new data about MCTD published in the last decade, to determine whether any new observations help to answer the conundrum of MCTD. After reviewing recent data, we question whether the term MCTD is appropriately retained, preferring to use the term undifferentiated autoimmune rheumatic disease. [ABSTRACT FROM AUTHOR]

Objective. To determine if ischaemia is a causal factor in the development of calcinosis in SSc. Methods. Patients with SSc were assessed yearly. Physicians reported the presence of calcinosis, digital ischaemia (digital ulcers, digital necrosis/gangrene, loss of digital pulp on any digits and/or auto- or surgical digital amputation) and nailfold capillary dropout assessed using a dermatoscope. The number of digits with digital ischaemia was used as an assessment of the severity of digital ischaemia. SSc specific antibodies were detected with a line immunoassay. Multiple logistic regression and Cox proportional hazards models were generated to determine associations between calcinosis, digital ischaemia and capillary dropout. Results. One thousand three hundred and five patients were included in this study, of whom 300 (23.0%) had calcinosis at study entry. In a cross-sectional multivariate analysis, at baseline, calcinosis was associated with digital ischaemia (odds ratio (OR) = 2.37, 95% CI: 1.66, 3.39), severity of ischaemia (OR = 1.12, 95% CI: 1.06, 1.18), capillary dropout (OR =1.41, 95% CI: 1.05, 1.89), ACAs (OR =1.68, 95% CI: 1.17, 2.43) and anti-RNA polymerase III antibodies (OR = 1.77, 95% CI: 1.08, 2.89). Current use of calcium channel blockers was inversely associated with the presence of calcinosis (OR = 0.70, 95% CI: 0.52, 0.96). Of the 805 patients with no calcinosis at study entry and at least one follow-up visit, 215 (26.7%) developed calcinosis during follow-up. Significant baseline predictors of the development of calcinosis in follow-up were digital ischaemia (hazard ratio (HR)= 1.82, 95% CI: 1.30, 2.54), capillary dropout (HR = 1.46, 95% CI: 1.08, 1.99), dcSSc (HR = 1.57, 95% CI: 1.11, 2.21), ACA (HR = 2.18, 95% CI: 1.50, 3.17) and anti-RNA polymerase III antibodies (HR = 2.58, 95% CI: 1.65, 4.04). Conclusion. Ischaemia may play a role in the development of calcinosis in SSc. [ABSTRACT FROM AUTHOR]

Objective. To propose simple capillaroscopic definitions for interpretation of capillaroscopic morphologies and to assess inter-rater reliability. Methods. The simple definitions proposed were: normal--hairpin, tortuous or crossing; abnormal --not hairpin, not tortuous and not crossing; not evaluable--whenever rater undecided between normal and abnormal. Based upon an aimed kappa of 0.80 and default prevalences of normal (0.4), abnormal (0.4) and not evaluable (0.2) capillaries, 90 single capillaries were presented to three groups of raters: experienced independent raters, n = 5; attendees of the sixth EULAR capillaroscopy course, n = 34; novices after a 1 -h course, n = 11. Inter-rater agreement was assessed by calculation of proportion of agreement and by kappa coefficients. Results. Mean kappa based on 90 capillaries was 0.47 (95% CI: 0.39, 0.54) for expert raters, 0.40 (95% CI: 0.36, 0.44) for attendees and 0.46 (95% CI: 0.41, 0.52) for novices, with overall agreements of 67% (95% CI: 63, 71), 63% (95% CI: 60, 65) and 67% (95% CI: 63, 70), respectively. Comparing only normal vs the combined groups of abnormal and not evaluable capillaries did increase the kappa: 0.51 (95% CI: 0.37, 0.65), 0.53 (95% CI: 0.49, 0.58) and 0.55 (95% CI: 0.49, 0.62). On the condition that the capillaries were classifiable, the mean kappa was 0.62 (95% CI: 0.50, 0.74) for expert raters (n = 65), 0.76 (95% CI: 0.69, 0.83) for attendees (n=20) and 0.81 (95% CI: 0.74, 0.89) for novices (n = 44). Conclusion. This multicentre, international study showed moderate reliability of simple capillaroscopic definitions for describing morphology of capillaries by rheumatologists with varying levels of expertise. Novices were capable of distinguishing normal from abnormal capillaries by means of a 1-h training session. In future studies, the class not evaluable may be obsolete. [ABSTRACT FROM AUTHOR]

Objectives. IL-35 is a member of the IL-12 family consisting of p35/IL-12a and EBI3/IL-27b subunits. IL-35 exerts immunomodulatory activities in experimental and human autoimmune inflammatory conditions. Our aim was to assess IL-35 expression in the skin and circulation of SSc patients and to characterize its potential association with SSc-related features. Methods. Expression of IL-35 in skin and dermal fibroblasts was quantified by quantitative PCR, immu-nohistochemistry and immunofluorescence. Serum levels of IL-35 (by ELISA), CRP (by turbidimetry), ANA (by immunofluorescence) and autoantibodies of the ENA complex (by immunoblot) were measured in 40 SSc patients. Serum IL-35 was determined in 40 age- and sex-matched healthy controls. Results. IL-35 expression was increased in SSc skin and dermal fibroblasts in a TGF-β-dependent manner. IL-35 induced an activated phenotype in resting fibroblasts and enhanced the release of collagen. IL-35 serum levels were increased in patients with SSc compared with healthy controls [median 83.9 (interquartile range 45.1-146.1) vs 36.2 (interquartile range 17.2-49.4) pg/ml, P< 0.0001]. Serum IL-35 was negatively correlated with disease duration (r= -0.4339, P = 0.0052). In line with this finding, serum IL-35 was increased in patients with an early SSc pattern on capillaroscopy assessment compared with those with active and late SSc patterns. Conclusion. The present study demonstrates overexpression of IL-35 in SSc skin, dermal fibroblasts and serum. TGF-β induces IL-35, which in turn activates resting fibroblasts and enhances the release of collagen, thereby contributing to aberrant TGF-β signalling in SSc. Increased serum IL-35 is associated with early, inflammatory stages of SSc. [ABSTRACT FROM AUTHOR]

Objectives. Nailfold videocapillaroscopy (NVC), the current gold standard for detection of capillary abnormalities suggestive of an SSc-spectrum disorder, is not widely available: a key question is whether lower-magnification, easy-to-use dermoscopy compares favourably. This is especially relevant given the inclusion of capillaroscopic abnormality within the 2013 classification criteria for SSc. Our objectives were to examine the ability to classify capillaries and to evaluate abnormality (severity), by both NVC and dermoscopy, to determine whether these differ between general and specialist rheumatologists, and to compare intra- and interrater reliability of both techniques. Methods. NVC and dermoscopy images were acquired from all 10 nailbeds of 32 subjects with a range of capillary abnormalities. Images were graded (using a web-based interface) on a 0-3 scale of severity: normal (0), mildly (1), definitely (2) and grossly abnormal (3), and an unclassifiable category. Raters graded images from four subjects (40 nailbeds) using each technique, with five repeated images to estimate intrarater reliability. Results. Forty-eight rheumatologists from 12 countries participated in the study (22 generalists, 26 specialists). While most images could be graded by both techniques, more were graded by NVC (84% vs 70%) and were systematically scored higher by NVC (mean difference 0.43 between the ratings). Agreement between the techniques was moderate. Intra- and interrater reliability were comparable for the two techniques in the classifiability of images and the grading of severity. Conclusion. Our results suggest that dermoscopy is comparable to NVC, although NVC images were more likely to be classifiable and were graded more severely. [ABSTRACT FROM AUTHOR]

Capillaroscopy is a non-invasive and safe tool to morphologically study the microcirculation. In rheumatology it has a dual use. First, it has a role in differential diagnosis of patients with RP. Second, it may have a role in the prediction of clinical complications in CTDs. In SSc, pilot studies have shown predictive associations with peripheral vascular and lung involvement hinting at a role of capillaroscopy as putative biomarker. Also and logically, in SSc, microangiopathy, as assessed by capillaroscopy, has been associated with markers of the disease such as angiogenic/static factors and SSc-specific antibodies. Moreover, morphological assessments of the microcirculation (capillaroscopy) seem to correlate with functional assessments (such as laser Doppler). Because of its clinical and research role, eyes are geared in Europe to expand the knowledge of this tool. Both the European League Against Rheumatism (EULAR) and the ACR are stepping forward to this need. [ABSTRACT FROM PUBLISHER]

Objective. Although findings of nail-fold capillary changes and reduced red blood cell velocity in SSc patients are well established, studies in adult-onset DM patients are scarce. Our objective was to assess the changes and red blood cell velocity in finger nail-fold capillaries using nail-fold video capillaroscopy (NVC) in patients with adult-onset DM.Methods. This study included 50 patients with adult-onset DM and 20 healthy subjects. A semi-quantitative rating scale was used to score capillaroscopy changes. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps.Results. Thirty-seven (74%) patients showed the scleroderma NVC pattern. Patients with the scleroderma pattern exhibited elevated serum creatine kinase levels more frequently and increased visual analogue scale of muscle disease activity. Scores of loss of capillaries were associated with muscle and global disease activity, whereas scores of haemorrhages were associated with skin disease activity. However, NVC findings were not significantly associated with lung involvement. The scores of irregularly enlarged capillaries, haemorrhages and loss of capillaries were reduced after stabilization of disease activity by treatment. The mean red blood cell velocity was not significantly reduced in DM patients compared with healthy controls and was not changed by treatment.Conclusion. Our results suggest that changes in nail-fold capillaries reflect disease activity in DM. Furthermore, the differences found in red blood cell velocity may reflect somewhat distinct microcirculation injuries in DM and SSc. [ABSTRACT FROM PUBLISHER]

Objective. To assess internal organ involvement in early SSc at presentation.Methods. One hundred and fifteen patients admitted to a tertiary centre because of RP, who did not present any routinely detectable scleroderma-related internal organ involvement, were investigated for ANA and videocapillaroscopy, and underwent history and physical examination to detect symptoms/signs suggestive of SSc. Patients were then subdivided into three groups: (i) early SSc, constituted by patients without clinical manifestations other than RP, but with scleroderma marker autoantibodies and/or typical capillaroscopic abnormalities; (ii) probable SSc, constituted by patients with the same autoantibody and/or capillaroscopic status as early SSc patients, but with any of the following manifestations: digital ulcers/scars, puffy fingers, arthritis, telangiectasia, dysphagia/heartburn, shortness of breath; (iii) UCTD, constituted by patients with a specific (i.e. disease antibody marker) ANA and capillaroscopic findings plus any disease manifestation. All patients were investigated by lung functional study and B-mode echo-Doppler-cardiography. Patients who consented underwent oesophageal manometry.Results. An inverted mitral E : A ratio (i.e. early scleroderma cardiac involvement) and/or a diffusing lung capacity for CO <80% of the predictive value (i.e. early lung involvement) and/or basal low oesophageal sphincter pressure <15 mmHg (i.e. early oesophageal involvement) were detected in 37/51 probable SSc patients (72%), 8/19 early SSc patients (42%) and 12/45 UCTD patients (27%).Conclusion. A scleroderma-related internal organ involvement was detected in patients from each group and, more importantly, was pre-clinical in a number of cases. [ABSTRACT FROM AUTHOR]

Objectives. Advances in nail-fold capillaroscopy allow capillary abnormalities to be quantified. Our aim was to investigate, in patients with SSc, the relationships between the degree of nail-fold capillary abnormality and disease subtypes (lcSSc and dcSSc), duration of RP and the presence of (i) severe digital ischaemia (as defined by previous i.v. vasodilators, debridements or amputations), (ii) a positive ACA, (iii) clinically evident calcinosis, (iv) pulmonary arterial hypertension and (v) telangiectases. [ABSTRACT FROM PUBLISHER]

Objective. The aim of this study was to test the hypothesis that statin therapy confers benefit on the microvasculature, including improving endothelial function, in patients with SSc. [ABSTRACT FROM PUBLISHER]

Objective. A simple weighted prognostic algorithm, based on capillaroscopy and autoantibodies, is developed to classify patients at different risk of transition from isolated RP to SSc within 5 years from the screening visit. [ABSTRACT FROM PUBLISHER]

Objective. Few rheumatologists have access to wide field or video capillaroscopy (abnormal capillaries being highly predictive of CTD), and a key question is whether they should, therefore, purchase a dermatoscope. The aim of this study was to estimate the inter- and intra-observer variability of dermoscopy (magnification 10×) among rheumatologists with little or no experience of the technique. Good reliability is a necessary prerequisite for a test to be a valid clinical or research tool. [ABSTRACT FROM PUBLISHER]

Objective. Local capillary permeability in patients with SSc has been reported increased when assessed by nail-fold capillaroscopy. We measured capillary permeability at a clinically less affected site by using large-window fluorescein videodensitometry of the ankle. We hypothesized that increased capillary permeability or leakage is a generalized phenomenon in SSc. [ABSTRACT FROM PUBLISHER]

Objective. To evaluate in a large group of scleroderma patients, the association of nailfold videocapillaroscopic patterns with both demographic and clinical features. [ABSTRACT FROM PUBLISHER]

Objective. Advanced glycation endproducts (AGEs), including Nɛ-(carboxymethyl)lysine-protein adducts (CML) are involved in micro/macrovascular changes and are co-localized with adhesion molecules in inflamed tissues. Serum levels of CML were investigated in systemic sclerosis (SSc) characterized by microvascular modifications and correlated with indices of micro/macrovascular damage.Methods. In 66 SSc patients (limited SSc, n = 55; diffuse SSc, n = 11) and 20 controls, CML serum levels were measured by enzyme-linked immunosorbent assay. Nailfold capillaroscopy, intima-media thickness (IMT) and the ankle-brachial index (ABI) were also recorded, to characterize micro/macrovascular involvement.Results. CML levels were significantly higher in SSc (79.2 ± 39 mg/ml vs 49.6 ± 26.1 mg/ml, mean ± s.d.; P<0.01), without significant differences between SSc subsets. CML levels were significantly higher in all capillaroscopic patterns: the ‘early’ pattern showed higher levels than ‘active’ and ‘late’ patterns. IMT was significantly higher in SSc (P<0.01) than in controls, whilst ABI was no different from controls.Conclusions. These data indicate that although both CML formation and macrovascular involvement are increased in SSc, there is no correlation between these two parameters. However, the characteristic early nailfold capillaroscopy changes of SSc are associated with proportionally greater CML formation, suggesting that AGEs are involved in SSc microangiopathy. [ABSTRACT FROM AUTHOR]

The difficulties inherent in diagnosing, screening and treating SSc are reflected by the complex pathology of the disease, which involves the development of severe organ-based complications that reduce both quality of life and overall survival. Early detection and prompt treatment of such complications depend upon a successful and timely screening strategy, which, in turn, requires cooperation between disciplines and good collaborative links at all stages of the disease. Establishment of a disease registry for SSc may also be of benefit, as such registries facilitate longitudinal observation of trends in disease presentation, management and outcome. They may also help to determine potential risk factors and identify those patient subgroups that face the highest risk of developing disease. In patients with known or suspected SSc, a panel of disease-specific markers—such as autoantibodies, cell activation markers and markers of organ involvement—may help to establish the diagnosis and assess prognosis; however, changes in serum levels of such markers throughout the course of SSc should be interpreted with caution, as they may not always correlate with disease activity. Nail-fold capillaroscopy is a promising tool for SSc assessment and may provide useful diagnostic and prognostic information, although further research is required to clarify its role in evaluating disease evolution. [ABSTRACT FROM PUBLISHER]